Creighton University's Hereditary Cancer Institute (CU), in three decades of study of hereditary cancer syndromes, has amassed a large resource of hereditary cancer families. We have the rapport with family members and the research experience to recruit members of these families for biomarker research. We have a large collection of biological specimens with extensive linked clinical and pedigree data. We will use these resources in collaborative biomarker research as a Clinical Epidemiology and Validation Center of the Early Detection Research Network (EDRN). As a member of the Network, our objectives will be: 1. To support EDRN collaborative studies by a. recruiting members of cancer-prone families for participation b. supplying specimens and associated data from our specimen repository 2. To maintain and expand our registry of individuals at high risk of specific cancer types who are willing to participate in biomarker studies. We will enroll individuals who are carriers of hereditary cancer syndrome associated germ-line mutations. 3. To develop a serum repository with annual samples recruited from high risk individuals. 4. To serve as a resource on hereditary cancer syndromes for other EDRN investigators. 5. To carry out the following research projects a. a study of the frequency of CDKN2A, MGMT, HLTF, APC, HIC1, p14 ARF, MINT31, MINT2, TIMP3, THBS1, and MLH1 methylation in Lynch syndrome colon adenomas and early colorectal cancers, and of the value of methylation assays of stool or serum DNA for detecting early methylation-positive colon neoplasms in Lynch syndrome patients. b. a study to evaluate the acceptability of hypothetical biomarkers among high risk and average risk individuals and primary health care providers. [unreadable] [unreadable]